Is nevirapine dose-escalation appropriate in young, African, HIV-infected children?

AIDS. 2013 Aug 24;27(13):2111-5. doi: 10.1097/QAD.0b013e3283620811.


Objectives: Young children metabolize nevirapine faster than older children/adults. We evaluated nevirapine pharmacokinetics with or without dose-escalation in Zambian, HIV-infected infants/children and its relationship with safety/efficacy.

Design: A retrospective pharmacokinetic substudy of the CHAPAS-1 trial.

Methods: HIV-infected, Zambian children were randomized to initiate antiretroviral therapy (ART) with full-dose twice-daily nevirapine versus 2-week nevirapine dose-escalation. Samples taken 3-4 h postmorning-dose 2 weeks after nevirapine initiation were assayed for nevirapine levels. Viral load was measured on available samples at weeks 4 and 48; adverse events were prospectively reported.

Results: Of 162 (77%) children with week-2 samples, 79 (49%) were randomized to nevirapine dose-escalation. At ART initiation, median [interquartile range (IQR)] age, weight and CD4% were 5.2 (1.5-8.7) years, 13.0 (8.1-19.0) kg and 13 (8-18)%, respectively; 81 (50%) were male. With full dose, few children aged less than 2 years (3/23, 13%) or more than 2 years (4/60, 7%) had subtherapeutic nevirapine levels (defined as <3.0 mg/l), but with dose-escalation, seven out of 22 (32%) aged less than 2 years versus seven out of 57 (12%) more than 2 years had subtherapeutic nevirapine levels (P=0.05). There was no difference between week-2 nevirapine levels in those with viral load more than 250 versus less than 250 copies/ml at week 4 (P=0.97) or week 48 (P=0.40). Eleven out of 162 children had grade 1/2 rash; all were more than 2 years of age (P=0.04), and 10 were randomized to full dose.

Conclusion: Subtherapeutic nevirapine levels 3-4 h postdose were more frequent in young children on dose-escalation. Younger children were at lower risk for rash. To simplify ART initiation and reduce the risk of suboptimal dosing, full-dose nevirapine at ART initiation should be considered for African HIV-infected children less than 2 years of age.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics*
  • Child
  • Child, Preschool
  • Exanthema / chemically induced
  • Exanthema / epidemiology
  • Female
  • HIV / isolation & purification
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Nevirapine / administration & dosage*
  • Nevirapine / adverse effects
  • Nevirapine / pharmacokinetics*
  • Retrospective Studies
  • Sequence Analysis, DNA
  • Viral Load
  • Zambia


  • Anti-HIV Agents
  • Nevirapine

Associated data

  • ISRCTN/ISRCTN31084535